Breadth and depth of working memory and executive function compromises in mild cognitive impairment and their relationships to frontal lobe morphometry and functional competence

INTRODUCTION: The extent of working memory (WM) and executive function (EF) impairment in mild cognitive impairment (MCI) is not well-characterized. METHODS: We compared 48 patients with MCI, 124 noncognitively impaired elderly healthy controls, and 57 patients with Alzheimer's disease (AD) on multiple WM/EF measures, frontal lobe integrity indexes, and functioning. RESULTS: Patients with MCI demonstrated worse performance on nearly all WM/EF tests. This profile of impairment was refined in a factor analysis that identified three primary WM/EF constructs: WM storage; speed and controlled visual search; and manipulation of information and problem solving. EF impairments were associated with reductions in prefrontal cortical thickness. WM/EF accounted for over 50% of the variance in functional competence. DISCUSSION: In MCI, WM/EF impairments are far from rare, based on specific compromises to frontal cortex circuitry, and are associated with loss of everyday functioning. WM/EF impairments, even at this potentially prodromal stage of AD, have clinically deleterious consequences.